Arterial embolization for massive bleeding from a locally advanced breast tumor.

Advances in breast cancer treatment have markedly reduced the incidence of massive bleeding, yet severe hemorrhage remains a critical issue in locally advanced or metastatic cases. Traditional management strategies often prove inadequate for significant bleeding, highlighting the need for alternative interventions. We detail the management of a 64-year-old patient with a neglected locally advanced breast tumor, leading to life-threatening hemorrhage. Conventional bleeding control measures failed, necessitating microsphere embolization. Effective hemostasis was achieved without adverse events or recurrence of bleeding, allowing for the initiation of chemotherapy. This case underscores the rarity yet potential severity of hemorrhage in breast cancer, challenging conventional management. Embolization, typically reserved for other hemorrhagic conditions, is appearing as a viable alternative for breast cancer-related hemorrhage, particularly in large tumors where surgery is impractical. Further research is necessary to establish its role in managing minor bleeding.

Neurogenic heterotopic ossification of the hip: Magnetic resonance imaging versus computed tomography for pre-surgical assessment.

PURPOSE: Neurogenic heterotopic ossification (NHO) of the hip is a frequent complication of spinal cord injuries, often requiring surgical management. Pre-surgical imaging assessment is essential, usually with computed tomography (CT)-scan. We aimed to compare magnetic resonance imaging (MRI) and CT for pre-surgical imaging assessment of the NHO, particularly for their relationships with vessels and nerves. METHOD: This prospective study included consecutive patients who underwent surgery for NHO from July 2019 to April 2022. All patients had CT angiography and MRI including Zero Echo Time and TRICKS sequences. Radiologists used standardized reports for CT and MRI to evaluate NHO and their features, bone mineralization, and relation to the arteries, veins and nerves. Agreement between pre-surgical CT and MRI was evaluated. RESULTS: Twenty-four patients (mean age: 53.5 ± 12.2 years) were included, among which 7 had bilateral NHO (31 hips). NHO were anterior in 15/31 hips (48 %), multifragmented in 25/31 hips (81 %). Mild and significant demineralization was most frequent. Gutter and tunnel were reported in 11.1 % of the arteries. Nerves were more often identified in MRI than in CT-scan. Agreement coefficients between CT and MRI were excellent for NHO location (0.95) and implantation (0.92), good for fragmentation (0.70), contact with joint capsule (0.66), bone mineralization (0.74), and relation to arteries (0.85), veins (0.76), sciatic nerve (0.7) and moderate for femoral nerve (0.47). CONCLUSION: MRI exhibited a good agreement with CT for pre-surgical assessment of NHO of the hip, especially to evaluate their relationships with the arteries, veins and sciatic nerve. Femoral nerves were more often identified in MRI than in CT-scan.

The multifaceted musculoskeletal hydatid disease.

Musculoskeletal hydatid disease is rare and can be located anywhere but most commonly the bone and muscles of the spine, pelvis, then the lower limbs. Imaging is essential for its diagnosis, performing the pre-therapeutic assessment, guiding possible percutaneous treatments, and providing post-therapeutic follow-up. Musculoskeletal hydatidosis can take several forms that may suggest other infections and tumors or pseudotumors. MRI and CT are superior for its diagnosis but ultrasound and radiography remain the most accessible examinations in developing countries where this parasitosis is endemic. In this review, we provide an overview of this disease and describe its different imaging patterns in soft tissue and bone involvement that should be sought to support the diagnosis.

The FLNC Ala1186Val Variant Linked to Cytoplasmic Body Myopathy and Cardiomyopathy Causes Protein Instability.

Filamin C-related disorders include myopathies and cardiomyopathies linked to variants in the FLNC gene. Filamin C belongs to a family of actin-binding proteins involved in sarcomere stability. This study investigates the pathogenic impact of the FLNC c.3557C > T (p.Ala1186Val) pathogenic variant associated with an early-onset cytoplasmic body myopathy and cardiomyopathy in three unrelated patients. We performed clinical imaging and myopathologic and genetic characterization of three patients with an early-onset myopathy and cardiomyopathy. Bioinformatics analysis, variant interpretation, and protein structure analysis were performed to validate and assess the effects of the filamin C variant. All patients presented with a homogeneous clinical phenotype marked by a severe contractural myopathy, leading to loss of gait. There was prominent respiratory involvement and restrictive or hypertrophic cardiomyopathies. The Ala1186Val variant is located in the interstrand loop involved in intradomain stabilization and/or interdomain interactions with neighbor Ig-like domains. 3D modeling highlights local structural changes involving nearby residues and probably impacts the protein stability, causing protein aggregation in the form of cytoplasmic bodies. Myopathologic studies have disclosed the prominent aggregation and upregulation of the aggrephagy-associated proteins LC3B and p62. As a whole, the Ala1186Val variant in the FLNC gene provokes a severe myopathy with contractures, respiratory involvement, and cardiomyopathy due to protein aggregation in patients' muscles.

Infectious sacroiliitis: MRI- and CT-based assessment of disease extent, complications, and anatomic correlation.

OBJECTIVE: To describe the frequency of MR and CT features of infectious sacroiliitis (ISI) and assess its extent and complications MATERIALS AND METHODS: This retrospective study included patients with ISI who were evaluated between 2008 and 2021 in a single center. Two radiologists reviewed MRI and CT images to determine the anatomical distribution (unilateral/bilateral, iliac/sacral bone, proximal/middle/distal), severity (bone marrow edema [BME]/periostitis/erosions), concurrent infection (vertebral/nonvertebral), and complications (abscess/probable adjacent osteomyelitis/cavitation/devitalized areas/sequestrum/pelvic venous thrombosis) of ISI. Interobserver reproducibility was assessed. Correlation analysis evaluated the effect of the causative microorganism on severity. Two human bodies were dissected to outline possible ways that ISI can spread. RESULTS: Forty patients with ISI (40 years ± 22; 26 women) were evaluated. Ten patients had bilateral ISI. Concurrent vertebral infection was associated in 15% of cases. Reproducibility of sacral BME, periostitis, and reactive locoregional abnormalities was perfect (κ = 1). Reproducibility was low for erosion count (κ = 0.52[0.52-0.82]) and periarticular osteopenia (κ = 0.50[0.18-0.82]). Inflammatory changes were BME (42/42 joints), muscle edema (38/42), and severe periostitis along the ilium (33/37). Destructive structural changes occurred with confluent erosions (iliac, 20/48; sacral, 13/48), sequestrum (20/48), and cavitation (12/48). Complications occurred in 75% of cases, including periarticular abscesses (n = 30/47), probable adjacent osteomyelitis (n = 16/37), and pelvic thrombophlebitis (n = 3). Tuberculous ISI (6/40) correlated with sclerosis (rs = 0.45[0.16; 0.67]; p < 10-2) and bone devitalization (rs = 0.38[0.16; 0.67]; p = .02). The anatomical study highlighted the shared venous vascularization of sacroiliac joints, pelvic organs, and mobile spine. CONCLUSION: Complications of ISI are frequent, including abscesses, adjacent osteomyelitis, and periostitis. ISI had bilateral involvement nonrarely and is commonly associated with another spinal infection.

An early onset benign myopathy with glycogen storage caused by a de novo 1.4 Mb-deletion of chromosome 14.

Early onset myopathies are a clinically and histologically heterogeneous monogenic diseases linked to approximately 90 genes. Molecular diagnosis is challenging, especially in patients with a mild phenotype. We describe a 26-year-old man with neonatal hypotonia, motor delay and seizures during infancy, and non-progressive, mild muscular weakness in adulthood. Serum Creatine kinase level was normal. Whole-body muscle MRI showed thin muscles, and brain MRI was unremarkable. A deltoid muscle biopsy showed glycogen storage. WGS revealed a de novo 1.4 Mb-deletion of chromosome 14, confirmed by Array-CGH. This microdeletion causes the loss of ten genes including RALGAPA1, encoding for RalA, a regulator of glucose transporter 4 (GLUT4) expression at the membrane of myofibers. GLUT4 was overexpressed in patient's muscle. Here we highlight the importance to search for chromosomal alterations in the diagnostic workup of early onset myopathies.

Hyper-fidelity depletion with discrete motion for pebble bed reactors.

Hyper-fidelity (HxF) depletion of pebble bed reactors (PBRs) is the capability to model depletion for every pebble while accounting for motion through the core. Previous HxF work demonstrated feasibility to deplete hundreds of thousands of stationary pebbles concurrently within reasonable timeframes. This work illustrates the second step towards HxF, coupling depletion with a discrete motion scheme. The model assumes an ordered bed with pebbles occupying fixed positions. Motion is simplified as discrete since pebbles move in straight lines from one set position to another. The methodology was implemented in Serpent 2, combined with its transport and depletion capabilities. Ad-hoc routines were developed ensuring compatibility with domain decomposition and pebble recirculation after each pass based on discharge criteria and fresh pebble insertion. Capabilities of HxF with discrete motion are demonstrated using a full-scale high-temperature gas-cooled reactor model. Specifically, an approach to equilibrium is performed, and example results are shown for in-core and discarded pebbles. The data illustrates how HxF provides unique insights into PBR fuel, producing information on statistical distributions rather than average values only, as obtained by traditional methods that rely on spectral zoning for depletion. Knowledge of these distributions can greatly improve analysis and assessment of PBRs.

Understanding a mass in the paraspinal region: an anatomical approach.

The paraspinal region encompasses all tissues around the spine. The regional anatomy is complex and includes the paraspinal muscles, spinal nerves, sympathetic chains, Batson's venous plexus and a rich arterial network. A wide variety of pathologies can occur in the paraspinal region, originating either from paraspinal soft tissues or the vertebral column. The most common paraspinal benign neoplasms include lipomas, fibroblastic tumours and benign peripheral nerve sheath tumours. Tumour-like masses such as haematomas, extramedullary haematopoiesis or abscesses should be considered in patients with suggestive medical histories. Malignant neoplasms are less frequent than benign processes and include liposarcomas and undifferentiated sarcomas. Secondary and primary spinal tumours may present as midline expansile soft tissue masses invading the adjacent paraspinal region. Knowledge of the anatomy of the paraspinal region is of major importance since it allows understanding of the complex locoregional tumour spread that can occur via many adipose corridors, haematogenous pathways and direct contact. Paraspinal tumours can extend into other anatomical regions, such as the retroperitoneum, pleura, posterior mediastinum, intercostal space or extradural neural axis compartment. Imaging plays a crucial role in formulating a hypothesis regarding the aetiology of the mass and tumour staging, which informs preoperative planning. Understanding the complex relationship between the different elements and the imaging features of common paraspinal masses is fundamental to achieving a correct diagnosis and adequate patient management. This review gives an overview of the anatomy of the paraspinal region and describes imaging features of the main tumours and tumour-like lesions that occur in the region.

Caveolinopathy: Clinical, histological, and muscle imaging features and follow-up in a multicenter retrospective cohort.

BACKGROUND AND PURPOSE: CAV3 gene mutations, mostly inherited as an autosomal dominant trait, cause various skeletal muscle diseases. Clinical presentations encompass proximal myopathy, distal myopathy, or isolated persistent high creatine kinase (CK) with a major overlapping phenotype. METHODS: Twenty-three patients with CAV3 symptomatic mutations, from 16 different families, were included in a retrospective cohort. Mean follow-up duration was 24.2 ± 15.0 years. Clinical and functional data were collected during the follow-up. The results of muscle imaging, electroneuromyography, muscle histopathology, immunohistochemistry, and caveolin-3 Western blot analysis were also compiled. RESULTS: Exercise intolerance was the most common phenotype (52%). Eighty percent of patients had calf hypertrophy, and only 65% of patients presented rippling. One patient presented initially with camptocormia. A walking aid was required in only two patients. Electroneuromyography was mostly normal. CK level was elevated in all patients. No patient had cardiac or respiratory impairment. Muscle imaging showed fatty involvement of semimembranosus, semitendinosus, rectus femoris, biceps brachialis, and spinal muscles. Almost all (87%) of the biopsies were abnormal but without any specific pattern. Whereas a quarter of patients had normal caveolin-3 immunohistochemistry results, Western blots disclosed a reduced amount of the protein. We report nine mutations, including four not previously described. No phenotype-genotype correlation was evidenced. CONCLUSIONS: Caveolinopathy has diverse clinical, muscle imaging, and histological presentations but often has limited functional impact. Mild forms of the disease, an atypical phenotype, and normal caveolin-3 immunostaining are pitfalls leading to misdiagnosis.

Elevation of brain ADC (apparent diffusion coefficient) in HIV-associated neurocognitive disorders and evolution after treatment: A pilot study.

BACKGROUND: Thirty to 50% of HIV-infected patients develop HIV-Associated Neurocognitive Disorders (HAND) despite virological control. The previously published Neuro+3 study showed their neurocognitive status can be improved by intensifying antiviral therapy. Our study is a part of the Neuro3+ study and aims to study apparent diffusion coefficient (ADC) as a biomarker for neurological improvement. PATIENTS AND METHODS: We prospectively included 31 patients with HAND. They received therapy with better CNS Penetration Effectiveness (CPE) score with two-year follow-up. Cognitive status was assessed at day 0 (D0) and week 96 (W96) using Frascati 3-stage classification and Global Deficit Score (GDS). Brain MRI at D0 and W96 assessed morphological data (white matter hyperintensities, opportunistic infections, ischemic lesions, atrophy) and measured whole brain apparent diffusion coefficient (ADC). We compared their data with a control group of 20 healthy patients with similar ages and sex ratio. RESULTS: After ARV intensification, cognitive status was significantly improved: GDS (n = 1,4 vs 1,0 p = 0.01) and Frascati scale (2HAD/22MND/7ANI vs 1HAD/8MND/17ANI p = 0.001). Mean ADC was significantly higher in patients at inclusion than in controls (0.88 × 10-3 mm2/s ± 0.06 vs 0.81 × 10-3 mm2/s ± 0.04, p = 0.0001). ADC decreased after treatment (0.88 × 10-3 mm2/s ± 0.06 vs 0.85 × 10-3 mm2/s ± 0.06 (p = 0,04). In subgroup analysis, ADC significantly decreased in clinically improved patients (0.89 × 10-3 mm2/s ± 0.07 vs 0.85 × 10-3 mm2/s ± 0.07 (p = 0,03)) and did not significantly change in non-clinically improved patients (0.86 × 10-3 mm2/s ± 0.07 vs 0.84 × 10-3 mm2/s ± 0.07 (p = 0,31)). After treatment, there was no significant difference between patients and controls (0.85 × 10-3 mm2/s ± 0.06 vs 0.81 × 10-3 mm2/s ± 0.04, p = 0.17). CONCLUSION: Whole-brain ADC is a good biomarker of HIV-associated neurocognitive disorders. It is significantly increased in patients with HAND compared with controls and significantly decreases after treatment. It is all the more important to have a quantitative biomarker as conventional imaging does not contribute to the diagnosis.

Heterotopic ossification and COVID 19: Imaging analysis of ten consecutive cases.

PURPOSE: Heterotopic ossification (HO) is defined by the formation of mature lamellar bone in periarticular soft tissue due to prolonged immobility. This study aimed to explore the imaging features of HOs in immobilized COVID-19 patients compared to other causes previously described in the literature. METHOD: This retrospective single centre study included patients with severe COVID-19 hospitalized in intensive care unit (ICU) with mechanical ventilation and affected by HOs between March 2020 and December 2021. Two radiologists reviewed imaging features of biphasic CT-scans using a standardized template including morphological findings and anatomical relationship of the HO with the joint, vessels and nerves. RESULTS: 10 COVID-19 patients with 19 analyzed HOs following ICU hospitalization were including. Biphasic CT imaging characteristics were analyzed. The hips were the most commonly affected joint (n = 14/19; 74%). The distribution was mainly posterior (n = 7/19; 38%). HOs were located away from main arteries. No case of severe demineralization was observed. Capsular disruption was observed for three HOs (n = 3/19; 16%). One patient presented concomitant venous thrombosis ipsilateral to the HO. CT-scan demonstrated neural involvement of the sciatic nerve in 3 patients with HO (n = 3/19; 16%). CONCLUSION: Severe COVID-19 patients with a biphasic CT imaging presented HO mainly located around the hips, with rare vessel and nerve invasion and no severe demineralization. Some features such as a lower level of local invasion differ from HOs related to other disorders as described in the literature whereas morphological aspects are similar.

Usefulness of Longitudinal Strain Adjusted to Regional Thickness in Hypertrophic Cardiomyopathy.

Background. We assessed the usefulness of a longitudinal strain adjusted to regional thickness in hypertrophic cardiomyopathy (HCM). Indeed, with conventional software, the width of the region of interest (ROI) is the same over the entire myocardial wall, wherein the software analyzes only partially the left ventricular (LV) hypertrophic segments. Methods. We included 110 patients: 55 patients with HCM (HCM group) and 55 healthy subjects (age- and sex-matched control group). The global longitudinal strain (GLS) and regional strain for each of the 17 segments was calculated with standard software (for two groups) and with software adjusted to the myocardial wall thickness (for the HCM group). Results. GLS was significantly decreased in the HCM group compared to the control group (−15.1 ± 4.8% versus −20.5 ± 4.3%, p < 0.0001). In the HCM group, GLS (standard method versus adjusted to thickness) measurements were not significantly different (p = 0.34). Interestingly, the regional strain adjusted to thickness was significantly lower than the standard strain in the hypertrophic segments, especially in the basal inferoseptal segment (p = 0.0002), median inferoseptal segment (p < 0.001) and median anteroseptal segment (p = 0.02). The strain adjusted to thickness was still significantly lower in the most hypertrophic segments (≥20 mm) (−3.7 ± 3%, versus −5.9 ± 4.4%, p = 0.049 in the basal inferoseptal segment and −5.7 ± 3.5% versus −8.3 ± 4.5%, p = 0.0007 in the median inferoseptal segment). In the segments with significant myocardial fibrosis, the longitudinal strain adjusted to thickness was significantly lower than the conventional strain (−8.3 ± 3.3% versus −11.4 ± 4.5%, p = 0.002). The analysis of the strain adjusted to thickness had a better feasibility (97.5% versus 99%, p = 0.01). Conclusions. The analysis of a longitudinal strain adjusted to regional thickness is feasible in HCM and allows a better evaluation of myocardial deformation, especially in the most LV hypertrophic segments.

Macroglossia: A potentially severe complication of late-onset Pompe disease.

BACKGROUND: Pompe disease is a rare neuromuscular disorder caused by a deficiency of a lysosomal enzyme, acid α-glucosidase. Macroglossia is a classic clinical sign of several inherited myopathies and has also been reported to occur progressively in late-onset Pompe disease (LOPD). METHODS: We describe patients with LOPD and macroglossia included in the French national Pompe disease registry. Clinical, functional, and radiological data were collected during periodic follow-up and analyzed retrospectively. These cases were compared with 15 previously reported cases. RESULTS: Five patients, three females and two males, aged 71-88 years, were included in this study. All but one of the patients suffered from symptoms related to macroglossia before the diagnosis of Pompe disease. Three had localized tongue atrophy and one had significant localized tongue hypertrophy which led to glossectomy 10 years before diagnosis. Two patients had severe dysphagia, one of whom underwent gastrostomy for enteral nutritional support. One patient experienced the persistence of numerous sleep apneas despite nocturnal bilevel positive airway pressure (BiPAP) ventilation. All our patients had dysarthria, and two required speech therapy. Four patients had a tongue hypersignal on magnetic resonance imaging (MRI) T1 sequences. CONCLUSIONS: Detection of macroglossia should be part of the clinical diagnosis and follow-up of patients with LOPD, with a careful evaluation of its main consequences. Macroglossia can have severe functional impacts on speech, swallowing, and sleep. Whole-body MRI with facial sections may facilitate the early diagnosis of Pompe disease with the "bright tongue sign".

Whole-body muscle MRI in McArdle disease.

This study describes muscle involvement on whole-body MRI (WB-MRI) scans at different stages of McArdle disease. WB-MRI was performed on fifteen genetically confirmed McArdle disease patients between ages 25 to 80. The degree of fatty substitution was scored for 60 muscles using Mercuri's classification. All patients reported an intolerance to exercise and episodes of rhabdomyolysis. A mild fixed muscle weakness was observed in 13/15 patients with neck flexor weakness in 7/15 cases, and proximal muscle weakness in 6/15 cases. A moderate scapular winging was observed in five patients. A careful review of the MRI scans, as well as hierarchical clustering of patients by Mercuri scores, pointed out recurrent muscle changes particularly in the subscapularis, anterior serratus, erector spinae and quadratus femoris muscles. WB-MRI imaging provides clinically relevant information and is a useful tool to orient toward the diagnosis of McArdle disease.

Comparison of magnetic resonance imaging and computed tomography for bone assessment of neurogenic heterotopic ossification of the hip: a preliminary study.

BACKGROUND: Neurogenic heterotopic ossification (NHO) is a frequent complication, often involving the hip. The functional impact may require surgical management and pre-surgical imaging assessment is necessary, usually by computed tomography (CT). We aimed to compare the performances of magnetic resonance imaging (MRI) and CT for bone assessment on pre-surgical imaging of the heterotopic ossifications and their features in NHO of the hip. METHODS: This single-center prospective preliminary study included all patients who underwent surgery for NHO with joint limitation from July 2019 to March 2020. All patients had a CT after biphasic iodinated solution injection and an MRI including T1-weighted, STIR and ZTE sequences. Standardized reports were completed for both exams for each patient, evaluating location, implantation and fragmentation of NHO, relation to the joint capsule and bone mineralization, then were compared. RESULTS: Seven patients from 32 to 70 years old (mean = 50.2 ± 17.2 years) were evaluated. NHO were bilateral in 2 patients, for a total of nine hips: six right hips and three left hips. Observed concordance rates between MRI and CT were, respectively, 94.4% for location, 100% for circumferential extension, 87.3% for implantation 88.9% for fragmentation, 77.8% for relation to the joint capsule and 66.7% for bone mineralization. It was 100% for femoral neck fracture and osteonecrosis of the femoral head. CONCLUSION: This preliminary study suggests that pre-surgical MRI imaging should be considered as effective as CT for bone assessment of NHO and their features. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03832556. Registered February 6, 2019, https://clinicaltrials.gov/ct2/show/NCT03832556 .

Assessing the accuracy of a new hand hygiene monitoring device (SmartRub®): from the laboratory to clinical practice.

BACKGROUND: We developed SmartRub® powered by iQati®, an electronic device composed of a wristband and an alcohol-based handrub pocket-sized dispenser that measures and provides feedback on the duration of hand friction and the volume poured during each hand hygiene action. We aimed to assess the accuracy of SmartRub®. METHODS: The specificity, sensitivity, positive and negative predictive values (PPV and NPV) of SmartRub® were assessed in a 3-phased experiment: (1) laboratory-controlled conditions with volunteers; (2) pre-planned clinical path with volunteers and (3) real clinical conditions with healthcare workers. The accuracy of SmartRub® was evaluated by quantifying its ability to correctly capture true hand hygiene actions and to not record other actions performed while wearing the device. RESULTS: In the laboratory, 7 volunteers performed 816 actions. Overall sensitivity was 94.1% (95% CI 91.4-96.2%) with a PPV of 99.0% (95% CI 97.3-99.6%) and specificity was 99.0% (95% CI 97.5-99.7%) with a NPV of 94.4% (95% CI 91.9-96.1%). During the pre-planned clinical path phase, 13 volunteers performed 98 planned paths and a total of 967 actions were performed. Overall sensitivity was 94.6% (95% CI 92.2-96.5%) with a PPV of 84.3% (95% CI 81.6-86.7%) and specificity was 82.4% (95% CI 78.7-85.7%) with a NPV of 93.9% (95% CI 91.3-95.7%). During the real clinical conditions phase, 17 healthcare workers were observed for a total of 15 h and 3 min while they performed 485 actions. Sensitivity was 96.8% (95% CI 93.8-98.6%) with a PPV of 98.3% (95% CI 95.6-99.3%) and specificity was 98.3% (95% CI 95.7-99.5%) with a NPV of 96.8% (95% CI 93.9-98.4%). CONCLUSIONS: Smartrub® is a highly reliable device for capturing hand hygiene actions under a range of conditions, from the laboratory to clinical care activities.

Beyond the sacro-Iliac joints: Vertebral involvement in axial spondylarthritis.

Imaging plays a central role in the diagnosis of axial spondylarthritis (axSpA). Commonly the sacroiliac joints are involved but vertebral involvement can occur in isolation in 1 out of 4 patients. Recognizing vertebral involvement patterns in axSpA can help establishing a diagnosis early and initiate therapy before irreversible changes have occurred. Magnetic resonance imaging (MRI) is considered the reference standard for early detection of inflammatory changes of the disease. Aims of this review are to present an overview of the imaging findings of vertebral involvement in axSpA, and to detail the current recommendations on the role of imaging in the diagnosis of axSpA in patients with isolated vertebral involvement.

INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH.

Marinesco-Sjögren syndrome is a rare human disorder caused by biallelic mutations in SIL1 characterized by cataracts in infancy, myopathy and ataxia, symptoms which are also associated with a novel disorder caused by mutations in INPP5K. While these phenotypic similarities may suggest commonalties at a molecular level, an overlapping pathomechanism has not been established yet. In this study, we present six new INPP5K patients and expand the current mutational and phenotypical spectrum of the disease showing the clinical overlap between Marinesco-Sjögren syndrome and the INPP5K phenotype. We applied unbiased proteomic profiling on cells derived from Marinesco-Sjögren syndrome and INPP5K patients and identified alterations in d-3-PHGDH as a common molecular feature. d-3-PHGDH modulates the production of l-serine and mutations in this enzyme were previously associated with a neurological phenotype, which clinically overlaps with Marinesco-Sjögren syndrome and INPP5K disease. As l-serine administration represents a promising therapeutic strategy for d-3-PHGDH patients, we tested the effect of l-serine in generated sil1, phgdh and inpp5k a+b zebrafish models, which showed an improvement in their neuronal phenotype. Thus, our study defines a core phenotypical feature underpinning a key common molecular mechanism in three rare diseases and reveals a common and novel therapeutic target for these patients.

Effect of Wearing a Novel Electronic Wearable Device on Hand Hygiene Compliance Among Health Care Workers: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Hand hygiene (HH) is essential to prevent hospital-acquired infections. Objective: To determine whether providing real-time feedback on a simplified HH action improves compliance with the World Health Organization's "5 Moments" and the quality of the HH action. Design, Setting, and Participants: This open-label, cluster randomized, stepped-wedge clinical trial was conducted between June 1, 2017, and January 6, 2018 (with a follow-up in March 2018), in a geriatric hospital of the University of Geneva Hospitals, Switzerland. All 12 wards and 97 of 306 eligible health care workers (HCWs) volunteered to wear a novel electronic wearable device that delivered real-time feedback on duration of hand rubbing and application of a hand-sized customized volume of alcohol-based handrub (ABHR). Interventions: This study had 3 sequential periods: baseline (no device), transition (device monitoring without feedback), and intervention (device monitoring and feedback). The start of the transition period was randomly allocated based on a computer-generated block randomization. Main Outcomes and Measures: The primary outcome was HH compliance, according to the direct observation method during intervention as compared with baseline. Secondary outcomes included the volume of ABHR and duration of hand rubbing measured by the device during intervention as compared with transition. Results: All wards and respective HCWs were evenly assigned to group 1 (26 participants), 2 (22 participants), 3 (25 participants), or 4 (24 participants). Twelve HCWs did not fully complete the intervention but were included in the analysis. During 759 observation sessions, 6878 HH opportunities were observed. HH compliance at intervention (62.9%; 95% CI, 61.1%-64.7%) was lower than at baseline (66.6%; 95% CI, 64.8%-68.4%). After adjusting for covariates, HH compliance was not different between periods (odds ratio, 1.03; 95% CI, 0.75-1.42; P = .85). Days since study onset (OR, 0.997; 95% CI, 0.994-0.998; P < .001), older age (OR, 0.97; 95% CI, 0.95-0.99; P = .015), and workload (OR, 0.29; 95% CI, 0.20-0.41; P < .001) were independently associated with reduced HH compliance. The median (interquartile range) volume of ABHR and duration of hand rubbing in transition and intervention increased from 1.12 (0.76-1.68) mL to 1.71 (1.01-2.76) mL and from 6.5 (4.5-10.5) seconds to 8 (4.5-15.5) seconds, respectively. There were no serious adverse events. Conclusions and Relevance: The use of this device did not change HH compliance, but increased the duration of hand rubbing and volume of ABHR used by HCWs. Trial Registration: isrctn.org Identifier: ISRCTN25430066.